Clinical Trial Protocol

Iranian Registry of Clinical Trials

17 Jul 2020

A randomized, two-armed, parallel, active-controlled clinical trial to

compare equivalent efficacy along with safety, and immunogenicity of
CinnaTropin® (CinnaGen, Iran) to Norditropin® NordiLet® (Novo Nordisk,
Denmark) in pre-pubertal children with growth hormone deficiency (GHD)

Protocol summary Daily injection of 0.03 mg/kg of CinnaTropin Daily

injection of 0.03 mg/kg of Norditropin NordiLet
Study aim Main outcome variables
This study aims to compare equivalent efficacy along Change in height velocity (cm/year)
with safety, and immunogenicity of CinnaTropin® to
Norditropin® NordiLet® in children with growth hormone
General information
deficiency.
Design Reason for update
This phase III study is a randomized, two-armed, parallel, Acronym
and active-controlled clinical trial to compare equivalent IRCT registration information
efficacy along with safety, and immunogenicity of IRCT registration number: IRCT20150303021315N12
CinnaTropin® to Norditropin® NordiLet® in pre-pubertal Registration date: 2019-04-07, 1398/01/18
children with growth hormone deficiency. Registration timing: registered_while_recruiting
Settings and conduct
This study will be conducted in 17 cities and 33 centers
in Iran. In this phase 3 study, after providing informed Last update: 2019-04-07, 1398/01/18
consent, 102 pre-pubertal patients with growth hormone Update count: 0
deficiency will be evaluated regarding inclusion and Registration date
exclusion criteria. After fulfilling the criteria patients will 2019-04-07, 1398/01/18
receive a randomization code, and be randomly assigned
to one of the arms of CinnaTropin or Norditropin Registrant information
NordiLet. Patients will receive the treatments for 12 Name
months. Nassim Anjidani
Participants/Inclusion and exclusion criteria Name of organization / entity
Inclusion Criteria:GH-naïve; Prepubertal; male children Orchid Pharmed
aged 3-10 and female children 3-8 years; Isolated Country
idiopathic growth hormone(GH) deficiency diagnosed; Iran (Islamic Republic of)
Peak GH<10.0µg/l following two recommended GH Phone
stimulation tests; Height Standard Deviation +98 21 4347 3000
Score(HSDS)≤-2.0 and Height Velocity SDS≤-1.0; or Email address
HSDS ≤ -3.0; bone age to chronological age ratio<0.9; amini@orchidpharmed.com
Full-term birth weight>2500g; Euthyroid. Exclusion
Recruitment status
Criteria: Chronic systemic disease; Evidence of active
recruiting
tumor; Chromosomal or skeletal abnormalities; Signs of
Funding source
idiopathic intracranial hypertension; Closed epiphyses;
Chronic use of oral or parenteral glucocorticoid in the last
three years; Using methylphenidate in the last 14 days Expected recruitment start date
Intervention groups 2018-12-14, 1397/09/23

1
Expected recruitment end date letters of the first name, first two letters of surname) and
2020-11-21, 1399/09/01 3 numbers (center code). Moreover, the code described
Actual recruitment start date is followed by the study unique identification code
empty consisting of first three letters of the name of the
Actual recruitment end date investigational product (which is CIN-) and three
empty numbers (corresponding to the randomization number),
Trial completion date e.g. ABCD001CIN-001. The randomization number will be
empty assigned in a consecutive way.
Blinding (investigator's opinion)
Scientific title Not blinded
A randomized, two-armed, parallel, active-controlled Blinding description
clinical trial to compare equivalent efficacy along with Placebo
safety, and immunogenicity of CinnaTropin® (CinnaGen, Not used
Iran) to Norditropin® NordiLet® (Novo Nordisk, Assignment
Denmark) in pre-pubertal children with growth hormone Parallel
deficiency (GHD) Other design features

Public title
Comparing CinnaTropin® with Norditropin® NordiLet® Secondary Ids
in pre-pubertal children with growth hormone deficiency
empty
Purpose
Treatment
Inclusion/Exclusion criteria
Ethics committees
Inclusion criteria:
GH-naïve Prepubertal (Tanner stage I) 3 to 10 years of 1
age for male children and 3 to 8 years of age for female
Ethics committee
children Isolated idiopathic growth hormone deficiency
Name of ethics committee
diagnosed Peak growth hormone value of <10.0 µg/l
Research Ethics Committee of Tehran University of
following two recommended growth hormone stimulation Medical Sciences
tests Height Standard Deviation Score (HSDS) ≤ -2.0 and Street address
Height Velocity Standard Deviation Score (HVSDS) ≤-1.0; Sixth floor, Research Deputy of Tehran University of
or HSDS ≤ -3.0 The ratio of bone age to chronological Medical Sciences, Ghods Street, Keshavarz Boulvard
age < 0.9 Full-term birth weight above 2500 g Euthyroid City
state Tehran
Exclusion criteria: Province
Chronic systemic disease, such as diabetes mellitus or Tehran
renal disease Evidence of active tumor Chromosomal or Postal code
skeletal abnormalities Signs of idiopathic intracranial 1417653761
hypertension Closed epiphyses Chronic use of oral or Approval date
parenteral glucocorticoid in the past three months Using 2018-08-25, 1397/06/03
methylphenidate in the last 14 days Ethics committee reference number
Age IR.TUMS.VCR.REC.1397.363
From 3 years old to 10 years old
Gender
Both
Health conditions studied

Phase
1
3
Groups that have been masked Description of health condition studied
No information Isolated idiopathic growth hormone deficiency
Sample size ICD-10 code
Target sample size: 102 E23.0
Randomization (investigator's opinion) ICD-10 code description
Randomized Hypopituitarism
Randomization description
The randomization plan of the patients will be carried out Primary outcomes
centrally using an R-CRAN software version 3.2.3. Blocks
(with the size 2 or 4) will be made using permuted block
randomization for a total of 102 patients (1:1 allocation 1
ratio). After the randomization procedure, a code will be Description
allocated to each patient that will be used as a patient- Change in height velocity
identifier throughout the study. The assigned code will Timepoint
be denoted by 4 initials (corresponding to the first two Prior to intervention and 12 months after the first

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 intervention 1
Method of measurement
Description
wall-mounted stadiometer
Control group: CinnaTropin® pen-injector (5 mg/1.5 mL,
CinnaGen, Iran), SC injection of 0.03 mg/kg for one year
Secondary outcomes Category
Treatment - Drugs

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2
Description
Change in height Description
Timepoint Control group: Norditropin® NordiLet® pen (5 mg/1.5
mL, Novo Nordisk, Denmark), SC injection of 0.03 mg/kg
Prior to intervention and 12 months after the first
for one year
intervention
Category
Method of measurement
Treatment - Drugs
wall-mounted stadiometer

Recruitment centers
2
Description
1
Change in weight
Timepoint Recruitment center
Prior to intervention and 12 months after the first Name of recruitment center
intervention Children's Medical Center
Method of measurement Full name of responsible person
Weight measuring device Dr. Ali Rabbani
Street address
Children's Medical Center, Dr. Mohammad Gharib
3 St.,Tehran
Description City
Tehran
Change in Height Standard Deviation Score (HSDS)
Province
Timepoint
Tehran
Prior to intervention and 12 months after the first
Postal code
intervention
1419733151
Method of measurement
Phone
Centers for Disease Control and Prevention clinical
+98 21 6694 9662
growth data Email
rabania@tums.ac.ir
4
Description 2
Safety Recruitment center
Timepoint Name of recruitment center
At screening visit, first intervention, and 3, 6, 9, and 12 Ali Asghar Children's Hospital
months after the first intervention Full name of responsible person
Method of measurement Dr. Maryam Razzaghi Azar
Patient’s history, physical examination, and laboratory Street address
data Ali Asghar Children's Hospital, Zafar St., Tehran
City
Tehran
5
Province
Description Tehran
Immunogenicity Postal code
Timepoint 1919816766
Prior to first intervention and at 3, 6, 9, and 12 months Phone
after the first intervention +98 21 2226 6846
Method of measurement Email
Evaluation of the presence and titre of anti-drug antibody dr.mnrbh@gmail.com
in the blood sample
3
Intervention groups Recruitment center

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 Name of recruitment center Name of recruitment center
Dr. Abdollah Dideban Clinic Dr. Shadab Salehpour Clinic
Full name of responsible person Full name of responsible person
Dr. Abdollah Dideban Dr. Shadab Salehpour
Street address Street address
Nili Aly., Naderi St.,Ghazvin No. 9, 225 BLDG., Gisha St., Tehran
City City
Tehran Tehran
Province Province
Tehran Tehran
Postal code Postal code
3413768414 1448833175
Phone Phone
+98 28 3335 3201 +98 21 2202 0996
Fax Fax
Email Email
drdidban@yahoo.com Shadab.salehpour@gmail.com

4 7
Recruitment center Recruitment center
Name of recruitment center Name of recruitment center
Dr. Robabeh Ghergherehchi Clinic Dr. Aria Sotoudeh Clinic
Full name of responsible person Full name of responsible person
Dr. Robabeh Ghergherehchi Dr. Aria Sotoudeh
Street address Street address
Iran Clinic BLDG., Abresan Square, Tabriz Mahan BLDG., Madaen Aly., Motahari St., Tehran
City City
Tabriz Tehran
Province Province
East Azarbaijan Tehran
Postal code Postal code
5156913183 1588764134
Phone Phone
+98 41 3334 9451 +98 21 8896 9783
Fax Fax
Email Email
ghergherehchir@yahoo.com arset59@yahoo.com

5 8
Recruitment center Recruitment center
Name of recruitment center Name of recruitment center
Dr. Mahtab Ordoei Clinic Dr. Mahin Hashemipour Zavareh Clinic
Full name of responsible person Full name of responsible person
Dr. Mahtab Ordoei Dr. Mahin Hashemipour Zavareh
Street address Street address
Zamani Aly., Taleghani Blvd., Yazd 152 BLDG., Bozorgmehr St., Isfahan
City City
Yazd Isfahan
Province Province
Yazd Isfehan
Postal code Postal code
8916697193 8158843134
Phone Phone
+98 35 3726 6860 +98 31 3267 4969
Fax Fax
Email Email
Dr.ordooei@yahoo.com mahin.hashemipour@yahoo.com

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Recruitment center Recruitment center

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 Name of recruitment center Full name of responsible person
Imam Reza Hospital Dr. Fahime Soheilipour
Full name of responsible person Street address
Dr.Hossein Moravej No. 1/2, Arman St., Gita Aly., Vanak St., Tehran
Street address City
Imam Reza Hospital، Namazi Square, Shiraz Tehran
City Province
Shiraz Tehran
Province Postal code
Fars 1435613613
Postal code Phone
7134814734 +98 21 8864 3998
Phone Fax
+98 71 3736 6268 Email
Email fsoheilipour@yahoo.com
Drmoravej@yahoo.com
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10 Recruitment center
Recruitment center Name of recruitment center
Name of recruitment center Dr. Reza Najafi Clinic
Dr. Heshmat Moayeri Clinic Full name of responsible person
Full name of responsible person Dr. Reza Najafi
Dr. Heshmat Moayeri Street address
Street address Adib Aly., Southern Sadi St., Ilam
No. 31, Yousef Abad 7th St., Tehran City
City Ilam
Tehran Province
Province Ilam
Tehran Postal code
Postal code 7633169319
1965834411 Phone
Phone +98 84 3333 6928
+98 21 8871 3068 Email
Fax rezan86@gmail.com
Email
Hmoayeri_endo@yahoo.com
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Recruitment center
11 Name of recruitment center
Recruitment center Dr. Fariba Ghasemi Clinic
Name of recruitment center Full name of responsible person
Mofid Children's Hospital Dr. Fariba Ghasemi
Full name of responsible person Street address
Dr. Mohammad Reza Alaei Razi BLDG., Shevari Aly., Shariati St., Tehran
Street address City
Mofid Children's Hospital, Shariati St., Tehran Tehran
City Province
Tehran Tehran
Province Postal code
Tehran 1965834422
Postal code Phone
1546815514 +98 21 2288 4356
Phone Email
+98 21 2222 7029 fariba.ghasemi@yahoo.com
Email
Alaee2003@yahoo.com
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Recruitment center
12 Name of recruitment center
Recruitment center Dr. Mohammad Reza Alaei Clinic
Name of recruitment center Full name of responsible person
Dr. Fahime Soheilipour Clinic Dr. Mohammad Reza Alaei

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 Street address Parsian BLDG., Shahid Heydarkhani Aly., Karaj
No. 11, Mina St., Shariati St., Tehran City
City Karaj
Tehran Province
Province Alborz
Tehran Postal code
Postal code 1416893458
1419733162 Phone
Phone +98 26 3270 9145
+98 21 2641 1643 Email
Email Sh.noorian@gmail.com
Alaee2003@yahoo.com
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16 Recruitment center
Recruitment center Name of recruitment center
Name of recruitment center Dr. Peyman Eshraghi Clinic
Dr. Fatemeh Sayarifard Clinic Full name of responsible person
Full name of responsible person Dr. Peyman Eshraghi
Dr. Fatemeh Sayarifard Street address
Street address Goharshad BLDG., Ghaem St., Ahmad Abad St.,
No. 119, Kosar BLDG., Keshavarz St., Tehran Mashhad
City City
Tehran Mashhad
Province Province
Tehran Razavi Khorasan
Postal code Postal code
1418765764 1545253612
Phone Phone
+98 21 6690 3940 +98 51 3844 2662
Fax Fax
Email Email
masiesayarifard@yahoo.com eshraghip2@mums.ac.ir

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Recruitment center Recruitment center
Name of recruitment center Name of recruitment center
Dr. Maryam Razzaghi Azar Clinic Dr. Nosrat Ghaemi Balhori Clinic
Full name of responsible person Full name of responsible person
Dr. Maryam Razzaghi Azar Dr. Nosrat Ghaemi Balhori
Street address Street address
No. 9, Southern Shahid Sarparast St., Felestin Square, Samen BLDG., Mohtashami St., Ahmad Abad St.,
Taleghani St., Tehran Mashhad
City City
Tehran Mashhad
Province Province
Tehran Razavi Khorasan
Postal code Postal code
1416893454 1523654891
Phone Phone
+98 21 6640 8796 +98 51 3841 7836
Email Fax
mrazar_md@yahoo.com Email
ghaemiN@mums.ac.ir
18
Recruitment center
21
Name of recruitment center Recruitment center
Dr. Shahab Norian Clinic Name of recruitment center
Full name of responsible person Dr. Elham Maleki Clinic
Dr. Shahab Norian Full name of responsible person
Street address Dr. Elham Maleki

6
 Street address City
Baran BLDG., Jahad St., Kerman Rasht
City Province
Kerman Guilan
Province Postal code
Kerman 2523216545
Postal code Phone
1364972585 +98 13 3313 1665
Phone Fax
+98 34 3221 5543 Email
Fax Dr.zaridoust@gmail.com
Email
pediatric18811@yahoo.com
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Recruitment center
22 Name of recruitment center
Recruitment center Dr. Hossein Ali Kharazmi Clinic
Name of recruitment center Full name of responsible person
Dr. Majid Aminzadeh Clinic Dr. Hossein Ali Kharazmi
Full name of responsible person Street address
Dr. Majid Aminzadeh Eram BLDG., Otoboos Rani St., Bandar Abbas
Street address City
Iran Zamin BLDG., Pahlavan St., Kianpars St.,Ahvaz Bandar Abbas
City Province
Ahvaz Hormozgan
Province Postal code
Khouzestan 1346973167
Postal code Phone
1416895264 +98 76 3363 4345
Phone Fax
+98 61 3336 1988 Email
Email kharazmi55403@yahoo.com
aminzadehmajid@yahoo.com
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23 Recruitment center
Recruitment center Name of recruitment center
Name of recruitment center Ali Asghar Children's Hospital
Dr. Fatemeh Safari Clinic Full name of responsible person
Full name of responsible person Dr. Maryam Nakhaei Moghadam
Dr. Fatemeh Safari Street address
Street address Ali Asghar Children's Hospital, Azadi St., Zahedan
Atiye BLDG., Booali St., Ghazvin City
City Zahedan
Ghazvin Province
Province Sistan-va-Balouchestan
Qazvin Postal code
Postal code 8954239641
1236987452 Phone
Phone +98 54 3322 9688
+98 28 3224 2579 Fax
Email Email
Drfa_saffari@yahoo.com maryamnakhaey@yahoo.com

24 27
Recruitment center Recruitment center
Name of recruitment center Name of recruitment center
Dr. Ahya Zaridost Clinic Dr. Peymaneh Sarkheil Clinic
Full name of responsible person Full name of responsible person
Dr. Ahya Zaridost Dr. Peymaneh Sarkheil
Street address Street address
Sina BLDG., Golsar St., Rasht Dadman St., Farahzadi St., Tehran

7
 City Province
Tehran Ghoum
Province Postal code
Tehran 5156913442
Postal code Phone
1425614981 +98 25 3290 7407
Phone Email
+98 21 8857 0612 javadshapouri@yahoo.com
Email
Peymaneh999@gmail.com
31
Recruitment center
28 Name of recruitment center
Recruitment center Dr. Seyedeh Tahereh Mousavi Clinic
Name of recruitment center Full name of responsible person
Dr. Kobra Shiasi Arani Clinic Seyedeh Tahereh Mousavi
Full name of responsible person Street address
Dr. Kobra Shiasi Arani Ehsan BLDG., Ashouri St., Yadegar Emam St., Bushehr
Street address City
Razi BLDG., Southern Iman St., Shahid Beheshti St., Bushehr
Kashan Province
City Boushehr
Kashan Postal code
Province 2587964130
Isfehan Phone
Postal code +98 77 3335 0431
8715981151 Email
Phone taheremousavi58@gmail.com
+98 31 5558 0189
Email
32
Kobra.shiasi@yahoo.com
Recruitment center
Name of recruitment center
29 Dr. Ali Rabbani Clinic
Recruitment center Full name of responsible person
Name of recruitment center Dr. Ali Rabbani
Dr. Siamak Shiva Clinic Street address
Full name of responsible person No. 6, Merikh Aly., North Kargar St., Tehran
Siamak Shiva City
Street address Tehran
Golgasht BLDG., Azadi St.,Tabriz Province
City Tehran
Tabriz Postal code
Province 1419733151
East Azarbaijan Phone
Postal code +98 21 6643 7006
5156913198 Email
Phone rabania@tums.ac.ir
+98 41 3358 9512
Email
33
Shivasiamak@yahoo.com
Recruitment center
Name of recruitment center
30 Dr. Majid Vares Vaziriyan Clinic
Recruitment center Full name of responsible person
Name of recruitment center Dr. Majid Vares Vaziriyan
Dr. Javad Shapouri Clinic Street address
Full name of responsible person Pastor BLDG.,1 Aly., Jahad St., Kerman
Javad Shapouri City
Street address Kerman
11 Aly., Amin Blvd., Qom Province
City Kerman
Qom Postal code

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 1364972599 City
Phone Tehran
+98 41 3223 3494 Province
Email Tehran
Dr.vazirian@gmail.com Postal code
1465884171
Phone
Sponsors / Funding sources
+98 21 8808 8821
Email
1 anjidani.N@orchidpharmed.com
Sponsor
Name of organization / entity Person responsible for scientific
CinnaGen company inquiries
Full name of responsible person
Dr. Somayeh Amini Contact
Street address Name of organization / entity
No 2, Khorasani deadend, Derakhti St, Dadman St, Orchid Pharmed Company
Shahrak-eGharb Full name of responsible person
City Dr. Somayeh Amini
Tehran Position
Province PharmD./Medical department manager
Tehran Latest degree
Postal code Medical doctor
1425614985 Other areas of specialty/work
Phone Medical Pharmacy
+98 21 4347 3000 Street address
Email No 2, Derakhti St, Dadman Blvd, shahrake Gharb
Amini.s@orchidpharmed.com City
Grant name Tehran
Grant code / Reference number Province
Is the source of funding the same sponsor Tehran
organization/entity? Postal code
Yes 1468813112
Title of funding source Phone
CinnaGen company +98 21 4347 3210
Proportion provided by this source Email
100 amini.s@orchidpharmed.com
Public or private sector
Private
Person responsible for updating data
Domestic or foreign origin
Domestic Contact
Category of foreign source of funding Name of organization / entity
empty Orchid Pharmed Company
Country of origin Full name of responsible person
Type of organization providing the funding Dr. Nasim Anjidani
Industry Position
Pharmacist, Clinical Trial Manager
Person responsible for general inquiries Latest degree
Medical doctor
Contact Other areas of specialty/work
Name of organization / entity Medical Pharmacy
Orchid Pharmed Company Street address
Full name of responsible person No.2, Derakhti St., Shahrak-e-Gharb, Tehran
Dr. Nasim Anjidani City
Position Tehran
Pharmacist, Clinical Trial Manager Province
Latest degree Tehran
Medical doctor Postal code
Other areas of specialty/work 1465884171
Medical Pharmacy Phone
Street address +98 21 8808 8821
No 2, Derakhti St., Shahrak-e-Gharb, Tehran, Iran Email

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 Anjidani.N@orchidpharmed.com make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to
Sharing plan make this available
Clinical Study Report
Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to
Undecided - It is not yet known if there will be a plan to
make this available
make this available Analytic Code
Study Protocol Undecided - It is not yet known if there will be a plan to
Undecided - It is not yet known if there will be a plan to make this available
make this available Data Dictionary
Statistical Analysis Plan Undecided - It is not yet known if there will be a plan to
Undecided - It is not yet known if there will be a plan to make this available

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